Neurite-like structures induced by mevalonate pathway blockade are due to the stability of cell adhesion foci and are enhanced by the presence of APP

作者：Hughes Mary; Snetkov Vladimir; Rose Ruth Sarah; Trousil Sebastian; Mermoud Jacqueline E; Dingwall Colin^*

来源：Journal of Neurochemistry, 2010, 114(3): 832-842.

DOI：10.1111/j.1471-4159.2010.06811.x

• adhesion
• amyloid precursor protein
• cerulenin
• mevalonate
• statins

P>Epidemiological studies have shown an association between statin use and a decreased risk of dementia. However, the mechanism by which this beneficial effect is brought about is unclear. In the context of Alzheimer's disease, at least three possibilities have been studied; reduction in amyloid beta peptide (A beta) production, the promotion of alpha-secretase cleavage and positive effects on neurite outgrowth. By investigating the effects of mevalonate pathway blockade on neurite outgrowth using real-time imaging, we found that rather than promote the production of neurite extensions, inhibition rapidly induced cell rounding. Crucially, neurite-like structures were generated through the persistence of cell-cell and cell-substrate adhesions and not through a mechanism of positive outgrowth. This effect can be strikingly enhanced by the over-expression of human amyloid precursor protein and is isoprenoid rather than cholesterol dependent.

• 出版日期2010-8